Research Findings - Epidemiology and Etiology Research

Highly active antiretroviral therapy (HAART) is often withheld from injection drug users (IDUs) infected with the human immunodeficiency virus (HIV) based on the belief that their unstable lifestyles may predetermine a markedly inferior outcome with HAART. However, long-term evaluations of HIV treatment outcomes among IDUs in comparison with other risk groups have not yet been available. Researchers compared survival rates among HIV-infected patients initiating HAART with and without a history of injection drug use. They used data from a population-based, prospective cohort study of 3116 antiretroviral-naive HIV-infected patients in a province-wide HIV/AIDS treatment program in British Columbia, Canada. Of the 3116 patients, 915 were IDUs (29.4%), 579 were female (18.6%), and the median age was 39.4 years (interquartile range, 33.3-46.4 years). Treatment with HAART was initiated between August 1, 1996, and June 30, 2006. The median duration of follow-up was 5.3 years (interquartile range, 2.8-8.3 years) for IDUs and 4.3 years (interquartile range, 2.0-7.6 years) for non-IDUs. Patients were followed up until June 30, 2007. Data were analyzed between November 1, 2007, and May 26, 2008. The main outcome measure was all-cause mortality. Overall, 622 individuals died (20.0%) during the study period (232 IDUs and 390 non-IDUs), for a crude mortality rate of 20.0% (95% confidence interval [CI], 18.4%-21.5%). At 84 months after the initiation of HAART, the product limit estimate of the cumulative all-cause mortality rate was similar between the 915 IDUs (26.5%; 95% CI, 23.2%-29.8%) and 2201 non-IDUs (21.6%; 95% CI, 16.9%-26.2%) (Wilcoxon P = .47). In multivariate time-updated Cox regression, the hazard ratio of mortality was similar between IDUs and non-IDUs (1.09; 95% CI, 0.92-1.29). These findings indicate that, in this study population, injection drug use was not associated with decreased survival among HIV-infected patients initiating HAART. Wood, E., Hogg, R., Lima, V., Kerr, T., Yip, B., Marshall, B., and Montaner, J. Highly Active Antiretroviral Therapy and Survival in HIV-Infected Injection Drug Users. JAMA, 300(5), pp. 550-554, 2008.

A Randomized Intervention Trial to Reduce the Lending of Used Injection Equipment among Injection Drug Users Infected with Hepatitis C

Researchers evaluated the efficacy of a peer-mentoring behavioral intervention designed to reduce risky distributive injection practices (e.g., syringe lending, unsafe drug preparation) among injection drug users with hepatitis C virus (HCV) infection. A randomized trial with a time-equivalent attention-control group was conducted among 418 HCV-positive injection drug users aged 18 to 35 years in 3 US cities (n=222 to intervention; n=196 to control). Almost half (47%) were recruited in Baltimore and about 1/4th from New York City (28%) and Seattle (25%). Participants reported their injection-related behaviors at baseline and at 3- and 6-month follow-ups. Compared with the control group, intervention-group participants were less likely to report distributive risk behaviors at 3 months (odds ratio [OR]=0.46; 95% confidence interval [CI]=0.27, 0.79) and 6 months (OR=0.51; 95% CI=0.31, 0.83), a 26% relative risk reduction, but were no more likely to cite their HCV-positive status as a reason for refraining from syringe lending. Effects were strongest among intervention-group participants who had known their HCV-positive status for at least 6 months. Peer mentoring and self-efficacy were significantly increased among intervention-group participants, and intervention effects were mediated through improved self-efficacy. This behavioral intervention reduced unsafe injection practices that may propagate HCV among injection drug users. Latka, M., Hagan, H., Kapadia, F., Golub, E., Bonner, S., Campbell, J., Coady, M., Garfein, R., Pu, M., Thomas, D., Thiel, T., and Strathdee, S. A Randomized Intervention Trial to Reduce the Lending of Used Injection Equipment among Injection Drug Users Infected with Hepatitis C. Am. J. Public Health, 98(5), pp. 853-861, 2008.

MAOA Methylation and Substance Dependence in Women

In recent years, the role of epigenetic phenomena, such as methylation, in mediating vulnerability to behavioral illness and in explaining gene-environment interplay have become increasingly appreciated. One prominent locus at which epigenetic phenomena are thought to be in play is the monoamine oxidase A (MAOA) locus. In order to examine the role of methylation at this locus, the authors performed quantitative methylation analysis across the promoter region of this gene in lymphoblast lines derived from 191 subjects (95 male, mean age 42; 96 female, mean age 39) participating in the Iowa Adoption Studies (IAS). They analyzed the resulting data with respect to genotype and lifetime symptom counts for the more common major behavioral disorders in the IAS, antisocial personality disorder (ASPD), and substance use disorders (alcohol (AD) and nicotine dependence (ND)). Methylation status was significantly associated with lifetime symptom counts for ND (P < 0.001) and AD (P < 0.008) in women, but not men. Furthermore, a trend was found for women homozygous for the 3,3 allele to have a higher degree of overall methylation than women homozygous for the 4,4 allele (P < 0.10). The authors conclude that methylation of MAOA may play a significant role in common psychiatric illness and that further examination of epigenetic processes at this locus is in order. Philibert, R., Gunter, T., Beach, S., Brody, G., and Madan, A. MAOA Methylation is Associated with Nicotine and Alcohol Dependence in Women. Am. J. Med. Genet. B Neuropsychiatr. Genet, 147B(5), pp. 565-570, 2008.

Correlates of Smoking Cessation in a Nationally Representative Sample of U.S. Adults

Persistent cigarette smoking is associated with significant morbidity and mortality. Correlates of difficulty quitting smoking include psychopathology, such as major depressive disorder, and problems with other substances, such as alcoholism. In addition, socio-demographic risk (e.g., poverty) and protective influences (e.g., living in a region with stringent tobacco laws) can modify risk for persistent cigarette smoking. Using data on 17,919 individuals with a lifetime history of smoking 100 or more cigarettes, from a nationally representative U.S. sample, the authors examine the constellation of risk and protective factors that correlate with smoking cessation (defined as remaining smoke-free in the past 12 months) across four cohorts: young (18-31 years), intermediate-aged (32-43 years), middle-aged (44-60 years) and older (61-99 years) adults. Using survival analyses, they demonstrate that in addition to a history of DSM-IV nicotine dependence, which is negatively associated with smoking cessation, living below the poverty line is also associated with persistent smoking across all age cohorts. Residents over the age of 31 years living on the U.S. West Coast are less likely to be persistent smokers as well. Major depressive disorder is associated with persistent smoking, but interestingly, only in middle-aged and older adults. Alcoholism and a family history of substance use problems are both correlated with persistent smoking but only in older adults. The authors suggest that psychopathology may hinder successful quit attempts during the developmental period when a majority of quit attempts are made (early to mid- 40's). However, the analyses also highlight the important benefits of effective tobacco legislation on the U.S. West Coast and suggest policy makers actively consider addressing issues surrounding tobacco taxation and the impact of poverty on tobacco use, in addition to the risks posed by co-occurring psychiatric problems and other substance use disorders. Agrawal, A., Sartor, C., Pergadia, M., Huizink, A., and Lynskey, M. Correlates of Smoking Cessation in a Nationally Representative Sample of US. Adults. Addict. Behav., 33(9), pp. 1223-1226, 2008.

Trends in Prescription Drug Abuse and Dependence, Co-occurrence with Other Substance Use Disorders, and Treatment Utilization

This study examined trends in prescription drug abuse and dependence (sedatives, tranquilizers, opioids, and stimulants), co-occurrence with other substance use disorders and substance abuse treatment utilization among those with diagnoses of prescription drug abuse and dependence in two large, nationally representative, samples of adults aged 18 and over in the United States in 1991-1992 and 2001-2002. National prevalence estimates were derived from the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey (n = 42,862) and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (n = 43,093). Data were collected from structured diagnostic interviews using the NIAAA Alcohol Use Disorder and Associated Disabilities Interview Schedule: Diagnostic and Statistical Manual version IV (DSM-IV). The past-year prevalence of prescription sedative abuse, sedative dependence, opioid abuse, and opioid dependence increased from 1991-1992 to 2001-2002. The majority of individuals with past-year sedative (56.8%), tranquilizer (89.0%), stimulant (67.9%) and opioid (74.2%) use disorders also met DSM-IV criteria for an additional past-year substance use disorder. The co-occurrence of several forms of prescription drug use disorders and other substance use disorders increased from 1991-1992 to 2001-2002. A minority of individuals with past-year prescription drug abuse and approximately one-half of those with past-year prescription drug dependence utilized substance abuse treatment. These findings reinforce the importance of continued national monitoring based on the increases in prescription drug abuse and dependence, high co-occurrence with other substance use disorders, and underutilization of substance abuse treatment services. McCabe, S., Cranford, J., and West, B. Trends in Prescription Drug Abuse and Dependence, Co-occurrence with Other Substance Use Disorders, and Treatment Utilization: Results from Two National Surveys. Addict Behav, 33(10), pp. 1297-1305, 2008.

Stimulant Treatment and Later Risk for SUDs

This study sought to examine the effects of early stimulant treatment on subsequent risk for cigarette smoking and substance use disorders (SUDs) in female adolescents with attention-deficit/hyperactivity disorder (ADHD). The authors used data from a case-controlled, prospective, 5-year follow-up study. Subjects were 114 female adolescents with ADHD originally ascertained from psychiatric and pediatric sources; mean age at follow up was 16.2 years; 94 had been treated with psychostimulants. The authors modeled time to onset of SUDs and smoking as a function of stimulant treatment. They found no differences in SUD risk factors between naturalistically treated and untreated groups other than family history of ADHD. Results indicated no increased risks for cigarette smoking or SUDs associated with stimulant therapy, and significant protective effects of stimulant treatment on the development of any SUD (hazard ratio [HR], 0.27; 95% confidence interval [CI], 0.13-0.60; P = .001) and cigarette smoking (HR, 0.28; 95% CI, 0.14-0.60; P = .001) that were maintained when controlling for conduct disorder. No effects of time to onset or duration of stimulant therapy on subsequent SUDs or cigarette smoking in subjects with ADHD were found. The authors conclude that stimulant therapy does not increase but rather reduces the risk for cigarette smoking and SUDs in female adolescents with ADHD, similar to their findings in boys. Other research by this group has shown that this reduction in SUDs is neutralized by adulthood, so it is possible that the stimulant therapy, if it has an effect, is delaying rather than preventing subsequent SUDs. Further research is awaited to address this important public health question. Wilens, T., Adamson, J., Monuteaux, M., Faraone, S., Schillinger, M., Westerberg, D., and Biederman, J. Effect of Prior Stimulant Treatment for Attention-Deficit/Hyperactivity Disorder on Subsequent Risk for Cigarette Smoking and Alcohol and Drug use Disorders in Adolescents. Arch. Pediatr. Adolesc. Med., 162(10), pp. 916-921, 2008.

Associations between Cigarette Smoking and ADHD

This study sought to evaluate the association between attention deficit hyperactivity disorder (ADHD) and severity of physical dependence on nicotine using a sample of adolescents and young adults with ADHD and controls. Data were drawn from two previous longitudinal case-control family studies of ADHD, and used self-reports on the modified Fagerstroem Tolerance Questionnaire (mFTQ) for degrees of physical dependence on nicotine. The final sample included 80 ADHD probands (43% male, mean age 19.3) and 86 control probands (38% female, mean age 19.2 years) on whom mFTQ data were available. The smokers with ADHD had significantly higher scores on the mFTQ, indicative of more severe physical dependence on nicotine. Similarly, in current smokers, a positive linear relationship was found between mFTQ score and both inattentive and hyperactive ADHD symptoms. Environmental factors, such as current parental smoking, peer smoking, and living with a smoker, all increased the risk for smoking in those with ADHD compared with controls. The authors conclude that male and female smokers with ADHD manifest more severe physical dependence on nicotine compared with controls, and that important environmental factors appear to add to the risk of smoking associated with ADHD. Wilens, T., Vitulano, M., Upadhyaya, H., Adamson, J., Sawtelle, R., Utzinger, L., and Biederman, J. Cigarette Smoking Associated with Attention Deficit Hyperactivity Disorder. J. Pediatr., 153(3), pp. 414-419, 2008.

Conduct Problems, Depressed Mood, and Adolescent Substance Use

Conduct problems are strong positive predictors of substance use and problem substance use among teens, whereas predictive associations of depressed mood with these outcomes are mixed. Conduct problems and depressed mood often co-occur, and such co-occurrence may heighten risk for negative outcomes. Thus, this study examined the interaction of conduct problems and depressed mood at age 11 in relation to substance use and problem use at age 18, and possible mediation through peer substance use at age 16. Analyses of multirater longitudinal data from a population-based sample of 429 rural youths (222 girls) and their families recruited and first interviewed in 1993 were conducted using a methodology for testing latent variable interactions. The link between the conduct problems x depressed mood interaction and adolescent substance use was negative and statistically significant. Unexpectedly, positive associations of conduct problems with substance use were stronger at lower levels of depressed mood. A significant negative interaction in relation to peer substance use also was observed, and the estimated indirect effect of the interaction on adolescent use through peer use as a mediator was statistically significant. These complex findings, some consistent with prior findings and some in contrast, illustrate the complexity of multiproblem youth. Mason, W., Hitchings, J., and Spoth, R. The Interaction of Conduct Problems and Depressed Mood in Relation to Adolescent Substance Involvement and Peer Substance Use. Drug Alcohol Depend., 96(3), pp. 233-248, 2008.

An Autosomal Linkage Scan for Cannabis Use Disorders in the Nicotine Addiction Genetics Project

Despite accumulating evidence that there is a genetic basis for cannabis use disorders (i.e., abuse and dependence), few studies have identified genomic regions that may harbor biological risk and protective factors. The researchers sought to conduct autosomal linkage analyses that identify genomic regions that may harbor genes conferring a vulnerability to cannabis use disorders. In 289 Australian families who participated in the Nicotine Addiction Genetics Project, 423 autosomal markers were genotyped. Families were ascertained for heavy cigarette smoking. Linkage analyses were conducted for DSM-IV cannabis dependence and for a novel factor score representing problems with cannabis use, including occurrence of 3 of 4 abuse criteria (excluding legal problems) and 6 DSM-IV dependence criteria. A maximum logarithm of odds (LOD) of 3.36 was noted for the cannabis problems factor score on chromosome arm 1p. An LOD of 2.2 was noted on chromosome 4 in the region of the gamma-aminobutyric acid type A gene cluster, including GABRA2, which has been implicated in drug use disorders. For DSM-IV cannabis dependence, a modest LOD score on chromosome 6 (1.42) near cannabinoid receptor 1 (CNR1) was identified. In addition, support for an elevation on chromosome 3, identified in prior independent studies, was noted for the factor score and cannabis dependence (LOD, 1.4). In conclusion, genes such as ELTD1 on chromosome 1, in addition to genes on chromosomes 4 (eg, GABRA2) and 6 (eg, CNR1), may be associated with the genetic risk for cannabis use disorders. The authors also introduce a novel quantitative phenotype, a cannabis problems factor score composed of DSM-IV abuse and dependence criteria, that may be useful for future linkage and association studies. Agrawal, A., Pergadia, M., Saccone, S., Lynskey, M., Wang, J., Martin, N., Statham, D., Henders, A., Campbell, M., Garcia, R., Broms, U., Todd, R., Goate, A., Rice, J., Kaprio, J., Heath, A., Montgomery, G., and Madden, P. An Autosomal Linkage Scan for Cannabis Use Disorders in the Nicotine Addiction Genetics Project. Arch. Gen. Psychiatry, 65(6), pp. 713-721, 2008.

Comorbidity of Psychiatric Disorders and Nicotine Dependence among Adolescents: Findings from a Prospective, Longitudinal Study

The authors examine prospectively the comorbidity of DSM-IV psychiatric disorders and nicotine dependence in adolescence. A multiethnic sample (N = 1,039) of adolescents from grades 6 to 10 in the Chicago public schools (mean age 14.1 years) was interviewed at home five times, and mothers were interviewed three times over a 2-year period (2003-2005). Completion rates at each wave were 96% of the initial sample. Selected DSM-IV psychiatric disorders were ascertained from youths and mothers about youths at two annual waves with the NIMH Diagnostic Interview Schedule for Children, Version IV-Y and IV-P; DSM-IV symptoms of nicotine dependence were ascertained from youths at every wave using a measure developed for adolescents. Psychiatric disorders most often preceded the onset of the first criterion of nicotine dependence. Prospective associations between psychiatric disorders and nicotine dependence were examined through logistic regressions. After controlling for comorbid disorders, it was found that lifetime disruptive disorder significantly predicted the onset of a nicotine dependence criterion (adjusted odds ratio 2.1). Early onset of any psychiatric disorder increased this risk. Other predictors included novelty seeking and extensiveness of smoking. By contrast, nicotine dependence did not predict the onset of a psychiatric disorder; significant predictors included the youths' prior other psychiatric disorders, novelty seeking, and parental depression and antisocial behavior. Nicotine dependence does not seem to contribute to the onset of psychiatric disorders, whereas disruptive disorder is an important etiologic factor for nicotine dependence in adolescence. Griesler, P., Hu, M., Schaffran, C., and Kandel, D. Comorbidity of Psychiatric Disorders and Nicotine Dependence among Adolescents: Findings from a Prospective, Longitudinal Study. J. Am. Acad. Child Adolesc. Psychiatry, 47(11), pp. 1340-1350, 2008.

Prevalence and Correlates of Jugular Injections among Injection Drug Users

Jugular injection of drugs has been reported although little is known about the prevalence of and risk factors associated with this behavior. Researchers used univariate statistics and logistic regression to examine factors associated with jugular injection among a cohort of injection drug users (IDU) in the Vancouver Injecting Drug Users Study (VIDUS), a large prospective cohort study of IDU recruited through snowball sampling methods in Vancouver, Canada. Between December 2004 and November 2005, 780 IDU were followed up as part of VIDUS and 198 (25%) reported jugular injection in the previous 6 months. In multivariate analyses, factors independently associated with jugular injection included being of the female gender [adjusted odds ratio (aOR) = 1.72, 95% confidence interval (CI): 1.14-2.59; p = 0.010], daily heroin use (aOR = 2.89, 95% CI: 1.93-4.34; p < 0.001), daily cocaine use (aOR = 1.76, 95% CI: 1.12-2.76; p = 0.014], requiring help injecting (aOR = 4.44, 95% CI: 2.64-7.46; p < 0.001), and involvement in the sex-trade (aOR = 2.71, 95% CI: 1.6-4.55; p < 0.001). These findings indicate that reporting a history of jugular injecting was alarmingly high in the cohort and significantly so among individuals with identifiable demographic and drug-using characteristics. Given previous reports demonstrating the risk of infection and vascular trauma due to this behavior, the findings underscore the need for interventions to reduce jugular injection and, for those who continue to inject, to provide information on safer injecting practices. Hoda, Z., Kerr, T., Li, K., Montaner, J., and Wood, E. Prevalence and Correlates of Jugular Injections among Injection Drug Users. Drug Alcohol Rev., 27(4), pp. 442-446, 2008.

A Twin Study of SES and Social Support following Illicit Drug Use

This study analyzed twin data to parse out the source of negative social attributes associated with drug use and abuse/dependence, asking if these associations may arise as a result of shared genetic or environmental factors rather than through causal pathways. The study used data from structured interviews conducted for 3969 male and female twins from the Mid-Atlantic Twin Registry and evaluations of their socioeconomic status (SES), social interactions, and use of drugs. Drug involvement was categorized as never used, tried, or met criteria for abuse or dependence. A co-twin control design was implemented using hierarchical linear modeling to assess whether twins who used drugs experienced lower SES and social support than non-using co-twins. Poorer social functioning in the drug-exposed twin would be consistent with a causal relationship, while similar functioning in the drug exposed versus naive twins would imply shared genetic or common environmental factors. Use of drugs was not significantly related to any SES measures. However, education and job status appear to share genetic influences with drug abuse/dependence. Lower income was not related to abuse/dependence of drugs. Negative interactions with friends and relatives share genetic factors with use of drugs, but the escalation from trying drugs to abusing them appears to generate discord between the abuser and friends and relatives in a causal fashion. These results indicate that presumptive causal influences of drug abuse/dependence on low SES may actually be mediated by shared genes. Drug use and social discord also appear to have shared genetic factors, but increased levels of drug involvement seem to causally influence social interactions. The authors discuss possible preventive implications of some presumptive causal mechanisms actually being due to shared liability. Bergen, S.E., Gardner, C.O., Aggen, S.H., and Kendler, K.S. Socioeconomic Status and Social Support Following Illicit Drug Use: Causal Pathways or Common Liability? Twin Res. Hum. Genet., 11(3), pp. 266-274, 2008.

Psychiatric Disorders Among Detained Youth

This study examined the prevalence of psychiatric disorders among youths transferred to adult criminal court and youths processed in the juvenile court. Participants were a stratified random sample of 1,829 youths, ten to 18 years of age, who were arrested and detained in Chicago. Data from version 2.3 of the Diagnostic Interview Schedule for Children were presented for 1,715 youths, 13 to 18 years of age, including 1,440 youths processed in juvenile court and 275 youths processed in adult criminal court. Males, African Americans, Hispanics and older youths had greater odds of being processed in adult criminal court than females, non-Hispanic whites and younger youths, even after the analyses controlled for felony-level violent crime. Among youths processed in adult criminal court, 68% had at least one psychiatric disorder and 43% had two or more types of disorders. Prevalence rates and the number of comorbid types of disorders were not significantly different between youths processed in adult criminal court and those processed in juvenile court. Among youths processed in adult criminal court, those sentenced to prison had significantly greater odds than those receiving a less severe sentence of having a disruptive behavior disorder, a substance use disorder or comorbid affective and anxiety disorders. Community and correctional systems need to be prepared to provide psychiatric services to youths transferred to adult criminal court and especially to youths sentenced to prison. Washburn, J., Teplin, L., Voss, L., Simon, C., Abram, K., and McClelland, G. Psychiatric Disorders among Detained Youths: A Comparison of Youths Processed in Juvenile Court and Adult Criminal Court. Psychiatr. Serv., 59(9), pp. 965-973, 2008.

Child Abuse and Risk for Cannabis Abuse

This study used an offspring of twins design to control for genetic environmental risk factors while examining the association between childhood physical abuse (CPA) and sexual abuse (CSA) and the development of cannabis abuse and dependence among adolescents and young adults. To control for familial risk differences related to paternal drug dependence that might confound the relationship between CSA and CPA and cannabis abuse/dependence, the authors created four groups based on father 's', and uncle 's' substance use dependence (SUD) status reflecting different degrees of genetic and environmental risks to offspring: (i) high genetic, high environmental risk; (ii) high genetic, low environmental risk; (iii) medium genetic, low environmental risk; and (iv) low genetic, low environmental risk. Participants included adolescent and young adult offspring of monozygotic and dizygotic US military veteran twin fathers (n = 819; 425 males, 394 females, mean age 23, interviewed in 2002-3). Data on CPA and CSA, DSM-IV offspring cannabis abuse/dependence, other SUD and psychopathology and maternal and paternal SUD and psychopathology were collected via semi-structured telephone interview. Twenty-three percent of the offspring sample met life-time criteria for cannabis abuse/dependence and 8.55% and 12.82% reported CSA and CPA, respectively. Offspring exposed to CSA, but not CPA, were at significantly greater risk of developing cannabis abuse/dependence compared to those who had not experienced CSA (hazard ratio = 2.16; 95% confidence interval = 1.48-3.16) after controlling for genetic and familial environmental risk and offspring gender, alcohol abuse and dependence and conduct disorder. The authors conclude that these results indicate that there are effects of CSA on development of cannabis abuse/dependence in addition to the genetic and familial environmental risk imparted by having a drug-dependent father. Duncan, A., Sartor, C., Scherrer, J., Grant, J., Heath, A., Nelson, E., Jacob, T., and Bucholz, K. The Association Between Cannabis Abuse and Dependence and Childhood Physical and Sexual Abuse: Evidence from an Offspring of Twins Design. Addiction, 103(6), pp. 990-997, 2008.

This study examined the prevalence, patterns, and correlates of adolescents' abuse, subthreshold dependence ("diagnostic orphans"), and dependence on prescription pain relievers (PPRs) such as opioids in a representative national sample (N = 36,992). Data were from the 2005-2006 National Surveys of Drug Use and Health. DSM-IV criteria for abuse and dependence were examined. Of all adolescents ages 12 to 17, 7% (n = 2,675) reported nonprescribed PPR use in the past year, and 1% (n = 400) met criteria for past-year PPR abuse or dependence. Among the 2,675 adolescents who reported nonprescribed PPR use, more than one in three reported symptoms of abuse or dependence: 7% abuse, 20% subthreshold dependence, and 9% dependence. Regular PPR use, major depressive episodes, and alcohol use disorders were associated with each diagnostic category. Compared with asymptomatic nonprescribed PPR users, increased odds of abuse were noted among nonstudents (adjusted odds ratio [AOR] 2.6), users of mental health services (AOR 1.8), and those reporting poor or fair health (AOR 2.4); and increased odds of dependence were observed among females (AOR 1.6), those who were involved in selling illicit drugs (AOR 1.7), and users of multiple drugs (AOR 2.9). Subthreshold dependent users resembled dependent users in major depressive episodes (AOR 1.5), alcohol use disorders (AOR 1.8), and use of multiple drugs (AOR 1.7). The study findings indicate that dependence on prescription pain relievers can occur without abuse. The authors stress that subthreshold dependence should be investigated further for consideration in major diagnostic classification systems. Wu, L., Ringwalt, C., Mannelli, P., and Patkar, A. Prescription Pain Reliever Abuse and Dependence Among Adolescents: A Nationally Representative Study. J. Am. Acad. Child Adolesc. Psychiatry, 47(9), pp. 1020-1029, 2008.

HIV Risk Among Youth in the Justice System

This study examines the prevalence and persistence of 20 human immunodeficiency virus (HIV)/sexually transmitted infection (STI) sexual and drug use risk behaviors and to predict their occurrence in four mutually exclusive diagnostic groups of delinquent youths: major mental disorder (MMD), substance use disorder (SUD), comorbid MMD and SUD (MMD+SUD) and neither disorder. At the baseline interview, HIV/STI risk behaviors were assessed in 800 juvenile detainees, ages 10 to 18 years; youths were reinterviewed approximately 3 years later. The final sample (N = 689) includes 298 females and 391 males. The prevalence and persistence of HIV/STI risk behaviors were high in all of the diagnostic groups. Youths with an SUD at baseline were greater than 10 times more likely to be sexually active and to have vaginal sex at follow-up than youths with MMD+SUD and four times more likely to be sexually active and to have vaginal sex than youths with neither disorder. Youths with an MMD at baseline were less likely to have engaged in unprotected vaginal and oral sex at follow-up compared with youths with neither disorder, and with youths with an SUD. Youths with MMD+SUD were less likely to engage in unprotected oral sex compared with those with neither disorder. Irrespective of diagnostic group, delinquent youths are at great risk for HIV/STIs as they enter into adulthood. SUD increases risk. Because detained youths are released after approximately 2 weeks, their risk behaviors become a community health problem. Pediatricians and child and adolescent psychiatrists must collaborate with corrections professionals to develop HIV/STI interventions and ensure that programs started in detention centers continue after youths are released. Elkington, K., Teplin, L., Mericle, A., Welty, L., Romero, E., and Abram, K. HIV/Sexually Transmitted Infection Risk Behaviors in Delinquent Youth with Psychiatric Disorders: A Longitudinal Study. J. Am. Acad. Child Adolesc. Psychiatry, 47(8), pp. 901-911, 2008.

Inattention as a Key Predictor of Tobacco Use in Adolescence

Researchers examined inattention among children as a predictor of tobacco use in adolescence in a longitudinal cohort of 177 African American and White boys, originally assessed at ages 7 and 13 as part of the Pittsburgh Youth Study, a community sample, and followed yearly to young adulthood (age 20). The overall study retention rate was 93.8%. Changes in self-reported tobacco use were tested with marginal transitional regression models, using parent and teacher ratings of inattention, hyperactivity-impulsivity, and other psychopathology, along with other factors, as predictors. Inattention, but not hyperactivity-impulsivity, significantly predicted adolescent tobacco use and young adult daily tobacco use. Peer substance use, parental substance use, and conduct disorder also predicted increases in tobacco use. African American ethnicity was strongly protective against later tobacco use. These results support the hypothesis that problems of inattention in childhood have a key role in increased tobacco use in adolescence and young adulthood. Burke, J., Loeber, R., White, H., Stouthamer-Loeber, M., and Pardini, D. Inattention as a Key Predictor of Tobacco Use in Adolescence. J. Abnorm. Psychol., 116(2), pp. 249-259, 2007.

Adolescence Drug Use Associated with Increased Risk for SUD

The authors aimed to extend the literature on the association of early onset of drug use and estimated risk for developing a substance use disorder (SUD) by investigating the risk that recent onset of alcohol and cannabis use confers for developing a substance use disorder at each chronological age of adolescence and young adulthood (12-21-years-old). Using 2003 data on 27,708 subjects in this age range from the National Survey on Drug Use and Health, they computed separate risk indices for developing an alcohol and cannabis use disorder for recent (prior 2 years) alcohol and cannabis users, respectively, at each age from 12 to 21 years of age, and compared estimated risk to recent onsets users among respondents aged 22-26. The results indicated that onset of use during the teenage years was strongly linked to an elevated risk status. The odds ratio (OR) of having a prior year alcohol use disorder (AUD) among recent onset alcohol users was significantly elevated for youth at ages 14, 16, 17 and 18 (range of ORs=2.0-2.1) compared to the estimated risk for AUD among recent onset users aged 22-26. For cannabis, significantly elevated ORs were found for a cannabis use disorder (CUD) at each of teenage years (ages 12-18; range of ORs=3.9-7.2), when compared to older recent onset users (aged 22-26). The authors conclude that the data provide further epidemiological support that adolescence is a particularly vulnerable period for developing a SUD. Winters, K., and Lee, C. Likelihood of Developing an Alcohol and Cannabis use Disorder during Youth: Association with Recent Use and Age. Drug Alcohol Depend., 92(1-3), pp. 239-247, 2008.

Factors Associated with Geographic Migration among a Cohort of Injection Drug Users

Environmental Contributions to Cannabis Abuse in Twin Design

Genetic and environmental factors are known to contribute to cannabis abuse/dependence (CAD). The authors sought to determine the magnitude of the contribution from measured environmental variables to offspring cannabis dependence in a design that controls for familial vulnerability. Data come from a study of 725 twin members of the Vietnam Era Twin Registry, 720 of their biological offspring (age 18-32 years, almost half female) and 427 mothers interviewed beginning in 2002. Data were obtained on offspring perception of family and peer support and substance use behaviors and offspring CAD. After adjusting for familial risk, and environmental covariates, CAD was significantly more likely among male offspring (OR=2.73; 95% CI: 1.69-4.41). Offspring CAD was associated with reporting: siblings used illicit drugs (OR=3.40; 95% CI: 1.81-6.38), a few friends used drugs (OR=2.72; 95% CI: 1.04-7.09), a quarter or more friends used drugs (OR=8.30; 95% CI: 3.09-22.33) and one-half or more 12th grade peers used drugs (OR=3.17; 95% CI: 1.42-7.08). Perceived sibling, friend and school peer substance use are strongly associated with CAD in young adults even after accounting for latent familial risk and for multiple measured intra-family and extra-family environmental influences. However, the authors acknowledge that these data cannot distinguish between peer influence and peer selection, and thus gene-environment correlation cannot be ruled out; future analyses are planned to investigate this question. Scherrer, J., Grant, J., Duncan, A., Pan, H., Waterman, B., Jacob, T., Haber, J., True, W., Heath, A., and Bucholz, K. Measured Environmental Contributions to Cannabis Abuse/Dependence in an Offspring of Twins Design. Addict. Behav., 33(10), pp. 1255-1266, 2008.

Comorbidity and Course of Substance Use from 12 to 22

The present study sought to understand concurrent links among diagnoses of substance use disorders, internalizing disorders, and behavior disorders at age 18 as well as developmental trajectories of illicit substance use prior to and after this point. Using data from 585 participants (52% male) in the Child Development Project, this study examined comorbidity among substance use, behavior, and internalizing disorders at age 18 and trajectories of growth in illicit substance use from age 12 to age 22. In this community sample, meeting diagnostic criteria for comorbid internalizing disorders, a behavioral disorder (conduct disorder or oppositional defiant disorder) alone, or both internalizing and behavioral disorders predicted higher concurrent substance use disorders (abuse, dependence, or withdrawal). Meeting diagnostic criteria for an anxiety disorder alone or depression alone did not predict higher concurrent substance use diagnoses. Over time, youths with behavioral disorders at age 18 showed a pattern of increasing substance use across early adolescence and higher levels of substance use than those with no diagnosis at age 18. Substance use declines from late adolescence to early adulthood were observed for all groups. Similar to previous literature, substance use disorders were more highly comorbid with behavior disorders than with internalizing disorders at age 18, and behavior disorder and comorbid behavior-internalizing disorders at age 18 were related to trajectories characterized by steep increases in illicit substance use during adolescence and high rates of illicit substance use over time. Lansford, J., Erath, S., Yu, T., Pettit, G., Dodge, K., and Bates, J. The Developmental Course of Illicit Substance Use from Age 12 to 22: Links with Depressive, Anxiety, and Behavior Disorders at Age 18. J. Child Psychol. Psychiatry, 49(8), pp. 877-885, 2008.

Sex Risk Behaviors of Drug Users: a Dual Site Study of Predictors Over Time

Reducing sex risk behaviors among high-risk injection drug users (IDUs) and crack smokers is a continuing challenge for controlling the spread of HIV. In a longitudinal study of sexually active Puerto Rican IDUs and crack smokers in New York (n = 573) and Puerto Rico (n = 264), researchers examined baseline predictors of changes in sex risk (number of unprotected sex acts) at 6 month and 36-month follow-up interviews. In New York, predictors of higher sex risk were younger age, having primary partners, having more other sex partners, never exchanging sex, having lower self-efficacy for reducing sex risk behaviors, and being HIV-negative. These predictors were significant at both postbaseline periods. In Puerto Rico, short-term predictors included being male, having primary partners, never exchanging sex, lower sex risk norms and lower self-efficacy. However, only having primary partners was significant in longer-term behaviors. These findings suggest the need for enhancing self-efficacy and for developing risk reduction strategies related to community differences. Deren, S., Strauss, S., Kang, S., Colon, H., and Robles, R. Sex Risk Behaviors of Drug Users: A Dual Site Study of Predictors Over Time. AIDS Educ. Prev., 20(4), pp. 325-337, 2008.

Cannabis use and depression are two of the most prevalent conditions worldwide. Adolescent cannabis use is linked to depression in many studies, but the effects of adolescent cannabis involvement on young adult depression remain unclear and may differ for males versus females. In this cohort study of youth from a mid-Atlantic metropolitan area of the United States, repeated assessments from 1985 (at age 6 years) through 2002 (at age 21 years) were made for 1,494 individuals (55% female). Measured covariate differences between individuals with and without cannabis problems were controlled via propensity score techniques. The estimated risk of young adult depression for adolescents with cannabis problems was not significantly different from that for comparison adolescents for either females (odds ratio = 0.7, 95% confidence interval: 0.2, 2.3) or males (odds ratio = 1.7, 95% confidence interval: 0.8, 3.6). The evidence does not support a causal association linking adolescent-onset cannabis problems with young adult depression. Harder, V., Stuart, E., and Anthony, J. Adolescent Cannabis Problems and Young Adult Depression: Male-Female Stratified Propensity Score Analyses. Am. J. Epidemiol., 168(6), pp. 592-601, 2008.

Children Taking Risks: The Association with Cocaine and Other Drug Use by Young Adulthood

The authors evaluate the long-term predictive strength of a novel cartoon-based risk-taking trait assessment, which might prove to have utility in future research on mechanisms leading toward illegal drug involvement. The longitudinal study population originated as 2311 first-graders entering 19 elementary schools during two successive school years. The assessments started soon after the children entered primary school. The key response variable was participants' use of cocaine by the time of a young adult assessment. The authors found that for each standard deviation increase in the risk-taking scale there was a two-fold increase in the risk of becoming a cocaine user by young adulthood (estimated relative risk, RR=1.9; 95% confidence interval, CI=1.3, 2.7). Independently, onset of cannabis use by young adulthood was also predicted by risk-taking scale values, but use of legal drugs (alcohol and tobacco) was not. These long-span associations provide support for new research on very early risk-taking mechanisms that lead toward illegal drug involvement. Rios-Bedoya, C., Wilcox, H., Piazza, M., and Anthony, J. Children Taking Risks: The Association with Cocaine and Other Drug Use by Young Adulthood. Addict. Behav., 33(9), pp. 1154-1161, 2008.

With the possible exception of cigarette smoking, little attention is paid to substance abuse among men whose partner is pregnant. An understanding of men's patterns of substance use during their partner's pregnancy is necessary to identify critical periods for intervention to reduce children's exposure to paternal substance use. This study examined the relationship between pregnancy or partner's pregnancy and patterns of binge drinking, cigarette use, and marijuana use, desistance, and return to use over a 3-year period from age 21 to 24 years. Data were drawn from the Seattle Social Development Project, a longitudinal study of prosocial and antisocial behavior. 808 (412 male, 396 female) students entering 5th grade in participating schools in the fall of 1985 that consented to participate constitute the sample. Interviews were conducted yearly from ages 10 to 16, at ages 18, 21, and 24. The data used in this study were obtained from age 24 data. Event history calendars were administered at age 24 and were retrospective to 21 years. To provide temporal context, a series of questions about live events, work, and school history were asked. Reports of events were probed to identify the month and year in which they occurred, and repeated events were probed to identify the month and year of each occurrence. Pregnancy was deduced based on the birth date of the child. Men were as likely to binge drink during their partner's pregnancy as they were when their partner was not pregnant. In contrast, women were significantly less likely to binge drink during pregnancy compared with before or after pregnancy. Men were less likely to smoke when their partner was pregnant than they were when their partner was not pregnant. Similarly, women were less likely to smoke during pregnancy than they were before or after pregnancy. Men were as likely to use marijuana during their partner's pregnancy as they were when their partner was not pregnant. Women were less likely to use marijuana when they were pregnant than when they were not pregnant. Because of a return to cigarette smoking among men and to all three forms of substance use among women occurs so soon after birth, the first few months postpartum may provide a critical opportunity for intervention. Men's binge drinking and marijuana use were unaffected by their partner's pregnancy or by the birth of their child suggesting the importance of reaching new fathers-to-be with messages about the importance of stopping substance use during their partner's pregnancy. Reductions in substance use among fathers both during pregnancy and after the birth of their child may increase the probability that mothers will desist from substance use during pregnancy, decrease the probability that mothers will relapse to use postpartum, and reduce children's exposure to harmful substance use in the home environment. Bailey, J.A., Hill, K.G., Hawkins, J.D., Catalano, R.F., and Abbott, R.D. Men's and Women's Patterns of Substance Use Around Pregnancy. Birth, 35(1), pp. 50-59, 2008.

Validity of Self-reported Substance Use in Men who Have Sex with Men: Comparisons with a General Population Sample

The authors examined the validity of self-reported recent drug use in men who have sex with men (MSM). They obtained a probability sample of Chicago men who have sex with men (MSM; n=216) and administered urine and saliva drug testing after a self-administered interview. Analyses examined participation in drug testing, the agreement between self-reported past month drug use and drug test results, correlates of underreporting, and the relative utility of drug testing versus self-reports in identifying recent marijuana and cocaine use. For marijuana and cocaine, findings were compared with those obtained from a general population sample of men (n=241). More than three quarters of the participants in both samples provided at least one specimen for drug testing. Self reports in both samples showed a high degree of correspondence with drug tests for marijuana but not for cocaine. Sensitivity for cocaine use reporting was 60% for the MSM sample and 40% for the general-population men. Conditional kappa and sensitivity statistics for marijuana, cocaine, 3, 4 methylenedioxy methamphetamine (i.e., MDMA, "ecstacy"), and methamphetamine suggested that self reports among MSM are provided with a high degree of validity. Underreporting was a correlate of social class (education, income, and employment) in the general population but not in the MSM sample. The utility of drug testing was dependent on social class in the general population sample. The authors suggest that drug testing is feasible in epidemiological surveys of drug use. Self reports among MSM are at least as valid as those provided by a general population sample of men. In some instances (e.g., cocaine use), they may actually be of higher quality. Although the findings support the merit of epidemiological studies of MSM drug use that have relied completely on self-reporting, drug tests may be useful for clarifying club drug ingestion patterns. Fendrich, M., Mackesy-Amiti, M., and Johnson, T. Validity of Self-reported Substance Use in Men who Have Sex with Men: Comparisons with a General Population Sample. Ann. Epidemiol., 18(10), pp. 752-759, 2008.

Autosomal Linkage Analysis for Cannabis Use Behaviors in Australian Adults

Cannabis is the most commonly used illicit drug in developed and in developing nations. Twin studies have highlighted the role of genetic influences on early stages of cannabis use, such as a lifetime history of use, early-onset use and frequent use, however, there have been few genomic studies that have examined these phenotypes. Using data on 2,314 families consisting of 5,600 adult Australian offspring and their parents, all of whom were scanned using 1,399 unique autosomal markers, the authors conducted autosomal linkage analyses for lifetime history of cannabis initiation, early-onset cannabis use and frequency of use, using a variance components approach in the linkage package MERLIN. Suggestive evidence for linkage was found on chromosome 18 (logarithm of odds (LOD) 2.14 for frequency of use, LOD 1.97 for initiation, at 90-97cM) and also on chromosome 19 (LOD 1.92 for early-onset at 17cM). These LOD scores did not meet genome-wide significance. Further replication of these linkage regions in other samples will be required, although these initial results suggest further targeted efforts on chromosome 18 may yield interesting candidate genes for early stages of cannabis-related behaviors. Agrawal, A., Morley, K., Hansell, N., Pergadia, M., Montgomery, G., Statham, D., Todd, R., Madden, P., Heath, A., Whitfield, J., Martin, N., and Lynskey, M. Autosomal Linkage Analysis for Cannabis Use Behaviors in Australian Adults. Drug Alcohol Depend., 98(3), pp. 185-190, 2008.

Genetic and Environmental Contributions to Nicotine, Alcohol, and Cannabis Dependence in Male Twins

The authors sought to compute the common and specific genetic and environmental contributions to nicotine dependence (ND) alcohol dependence (AD) and cannabis dependence (CD), utilizing a twin model design for the study. Data from 1874 monozygotic and 1498 dizygotic twin pair members of the Vietnam Era Twin Registry were obtained via telephone administration of a structured psychiatric interview in 1992. Data to derive life-time diagnoses of DSM-III-R ND, AD and CD were obtained via telephone administration of the Diagnostic Interview Schedule. The best-fitting model allowed for additive genetic contributions and unique environmental influences that were common to all three phenotypes. Risks for ND and AD were also due to genetic and unique environmental influences specific to each drug. A specific shared environmental factor contributed to CD. These results suggest that the life-time co-occurrence of ND, AD and CD is due to common and specific genetic factors as well as unique environmental influences, and vulnerability for CD is also due to shared environmental factors that do not contribute to ND and AD. The majority of genetic variance is shared across drugs and the majority of unique environmental influences are drug-specific in these middle-aged men. Because differences between models allowing for specific genetic versus shared environment were small, the authors suggest that there are specific familial contributions-either additive genetic or shared environment-to CD. Xian, H., Scherrer, J., Grant, J., Eisen, S., True, W., Jacob, T., and Bucholz, K. Genetic and Environmental Contributions to Nicotine, Alcohol and Cannabis Dependence in Male Twins. Addiction, 103(8), pp. 1391-1398, 2008.

Hepatitis C virus (HCV) is hyper-endemic among injecting drug users, and increasingly so among non-injection drug users who smoke, snort, or sniff heroin, cocaine, crack, or methamphetamine. To summarize the research literature on HCV in drug users and identify gaps in knowledge, researchers conducted a synthesis of the relevant research carried out between 1989 and 2006. They used rigorous search methods to identify and extract data from published and unpublished reports of HCV among drug users. They designed a quality assurance system for all phases of the project and created a set of items to assess study design quality of each report that they included. In all, they found 629 reports containing HCV prevalence rates, incidence rates and/or genotype distribution among injecting or non-injecting drug user populations published between January 1989 and December 2006. The majority of reports were from Western Europe (41%), North America (26%), Asia (11%) and Australia/New Zealand (10%). They also identified reports from Eastern Europe, South America, the Middle East, and the Caribbean. The number of publications reporting HCV rates in drug users increased dramatically between 1989 and 2006, to 27-52 reports per year after 1998. The data collection and quality assurance phases of the HCV Synthesis Project have now been completed and are providing a rich source of information on HCV in drug users worldwide. Specifically, analyses are underway to understand HCV etiology relative to type of drug used and route of administration. Further, the project is able to examine data across a larger set of studies, which is especially important for HCV seroconversion studies that suffer from small sample sizes and low power to examine risk factors. Stern, R., Hagan, H., Lelutiu-Weinberger, C., Des Jarlais, D., Scheinmann, R., Strauss, S., Pouget, E., and Flom, P. The HCV Synthesis Project: Scope, Methodology, and Preliminary Results. BMC Med. Res. Methodol., 8, pp. 62-74, 2008.

Are There Genetic Influences on Addiction: Evidence from Family, Adoption and Twin Studies

In this era of gene discovery, the authors review evidence from family, adoption and twin studies that examine the genetic basis for addiction. With a focus on the classical twin design that utilizes data on monozygotic and dizygotic twins, they examine support in favor of heritable influences on alcohol, nicotine, cannabis and other illicit drug dependence. They review whether these genetic factors also influence earlier stages (e.g. experimentation) of the addictive process and whether there are genetic influences specific to each psychoactive substance. Converging evidence from these studies supports the role of moderate to high genetic influences on addiction. The changing role of these heritable factors as a function of gender, age and cultural characteristics is also discussed. The authors highlight the importance of the interplay between genes and the environment as it relates to risk for addiction and the utility of the children-of-twins design for emerging studies of gene-environment interaction is presented. Despite the advances being made by low-cost high-throughput whole genome association assays, the authors suggest that information garnered from twin studies, especially extended twin designs with power to examine gene-environment interactions, will continue to form the foundation for genomic research. Agrawal, A., and Lynskey, M. Are There Genetic Influences on Addiction?: Evidence from Family, Adoption and Twin Studies. Addiction, 103(7), pp. 1069-1081, 2008.